Clinical Trials Register

Summary
EudraCT Number:	2006-001843-74
Sponsor's Protocol Code Number:	DRI6738
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2006-06-21
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2006-001843-74

A.3

Full title of the trial

A randomized, double-blind, parallel-group, placebo-controlled, dose-response, multicentre, multinational study evaluating the efficacy and safety of AVE2268 administered either twice daily (breakfast and lunch) at a dose of 300, 600 and 1200 mg or once daily (breakfast) at a dose of 1200 mg, in patients with type 2 diabetes treated with metformin and not adequately controlled

A.4.1

Sponsor's protocol code number

DRI6738

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sanofi-Synthelabo Recherche
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	NA
D.3.2	Product code	AVE2268
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	647834-15-9
D.3.9.2	Current sponsor code	AVE2268
D.3.9.3	Other descriptive name	(3-(2-(4-methoxybenzyl)-thiophenyl)-β-D-glucopyranosid)
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Information not present in EudraCT
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	NA
D.3.2	Product code	AVE2268
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	647834-15-9
D.3.9.2	Current sponsor code	AVE2268
D.3.9.3	Other descriptive name	(3-(2-(4-methoxybenzyl)-thiophenyl)-β-D-glucopyranosid)
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	600
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Information not present in EudraCT

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Type 2 diabetes

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	8.1
E.1.2	Level	LLT
E.1.2	Classification code	10045242

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate the efficacy of AVE2268 in reducing mean plasma glucose calculated from 10-points plasma glucose profiles after a four-week treatment period.

E.2.2

Secondary objectives of the trial

To assess the effects of AVE2268 on fasting plasma glucose and 2-hour post prandial plasma glucose after standardized test breakfast, lunch and dinner test meals

To assess the safety and tolerabillity of AVE2268

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

see section "9.3 pharmacokinetics (selceted countries only)" of the DRI6738 protocol: PK plasma and urine investigation will be done in a subgroup of patients (approximately 25% of the total, i.e. 75 patients) recruited in a subset of centres.

see section "9.4 Genotyping" of the DRI6738 protocol: genotyping of clinically relevant polymorphisms in drug-metabolizing enzymes

E.3

Principal inclusion criteria

·Male or female patients aged ≥ 18 years and < 75 years at screening.
·Type 2 diabetes mellitus, as defined by the American Diabetes Association, for at least one year at the time of screening (Appendix A)
·HbA1c measured at visit 1 in the range of ≥ 7.0 and <or= 9.0 %;
·Stable metformin treatment (dose ≥ 1.5g/day for at least 3 months prior to enrollment in the study). No other antidiabetic medications are permitted for 3 months prior to enrollment
·Written informed consent/consents.

E.4

Principal exclusion criteria

- Modification of metformin treatment within 3 months prior to screening visit.
- BMI >40kg/m2
- Administration of other investigational drugs within 60 days prior to screening visit.
-Presence of any clinically significant endocrine disease (other than type 2 diabetes).
Note: euthyroid patients on replacement therapy can be included if the dosage of thyroxine is stable for at least 3 months prior to screening visit
- Diabetes other than type 2 diabetes
- Subjects with “brittle-diabetes” or any hospitalization or emergency room visit due to poor diabetic control within the past 6 months, previous history of diabetes related dehydration leading to hospitalization, history or evidence of ketoacidosis
- Presence or history of cancer within the past five years with the exception of adequately treated localized basal skin cancer or in situ uterine cervical cancer
- History or presence of pancreatitis
- Evidence of clinically relevant uncontrolled hypertension
- Evidence within the past 6 months of myocardial infarction, stroke, retinopathy requiring laser surgery, or heart failure requiring hospitalization
- Positive test for hepatitis B surface antigen and/or hepatitis C antibody
- Impaired hepatic tests as shown but not limited to ALT, AST > 3 x ULN, AP > 2 x ULN and Bilirubin >1.5 x ULN
If Bilirubin is >1.5 ULN, and all other liver parameters are within the limits described above, a measurement of direct and indirect Bilirubin will be done to diagnose a potential Gilbert's disease which will not be an exclusion criteria
- Impaired renal function, as shown but not limited to creatinine clearance < 50 ml/min (predicted by using the Cockcroft-Gault formula)
- History of proteinuria >1g/24h or presence at screening of a protein : creatinine ratio > 0.7 (g protein: mmol creatinine) in the absence of excessive exercise
- Presence of urinary tract infection at screening
- Presence of any clinically significant abnormality in blood or urinary laboratory tests performed at screening
- Presence of any clinically significant abnormality on the ECG performed at the screening visit
- Treatment with other antidiabetic agents (including insulin) other than metformin in the last 3 months before study entry
- Prolonged use (more than 10 days) of systemic corticosteroids (or if daily dosage> 1000 μg equivalent beclomethasone) within the past 3 months or administration of systemic long-acting corticosteroids within the past 3 months or anticipated need for systemic glucocorticoids during the study
-Thyroid replacement therapy if the dosage has been modified during the 3 months prior to screening visit.
- Pregnant or breast-feeding women
- Women of childbearing potential not protected by medically approved contraceptive method of birth control, or who are unwilling or unable to be tested for pregnancy. Pregnancy status should be checked by serum pregnancy testing prior to exposure to the investigational product and at the end of the study.
- History or evidence of clinically relevant renal or urological disorder (i.e. obstructive renal disease, prostatic disorder with significant impact on miction, primary glomerular diseases...), significant hematuria (++ quantitatively assessed)
- History or presence of gastrointestinal disorder, i.e. chronic diarrhea, stomach/gastric surgery, irritable bowel syndrome

E.5 End points

E.5.1

Primary end point(s)

Change in Mean Plasma Glucose (MPG) from baseline to week 4 calculated from 10-point profiles (before, 90 and 120 min after standardized breakfast, lunch and dinner test meals and at bedtime)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Information not present in EudraCT

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Information not present in EudraCT

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Information not present in EudraCT

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Information not present in EudraCT

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.5

The trial involves multiple Member States

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Information not present in EudraCT
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	40
F.4.2	For a multinational trial
F.4.2.1	In the EEA	130
F.4.2.2	In the whole clinical trial	300

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2006-11-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-10-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2008-01-07

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